Finite Axiomatisability of Subdirectly Irreducible Members of Certain Nilpotent Varieties

Let $\mathcal{V}$ be a congruence permutable variety generated by a finite nilpotent algebra $\mathbf{A}$. If $\mathbf{A}$ is a product of algebras of prime power order, then the class $\mathcal{V}_\text{si}$ of subdirectly irreducible members of $\mathcal{V}$ can be axiomatised by a finite set of elementary sentences

Checkpoint Inhibition Reduces the Threshold for Drug-Specific T-Cell Priming and Increases the Incidence of Sulfasalazine Hypersensitivity

An emerging clinical issue associated with immune-oncology agents is the collateral effects on the tolerability of concomitant medications. One report of this phenomenon was the increased incidence of hypersensitivity reactions observed in patients receiving concurrent immune checkpoint inhibitors (ICIs) and sulfasalazine (SLZ). Thus, the aim of this study was to characterize the T cells involved in the pathogenesis of such reactions, and recapitulate the effects of inhibitory checkpoint blockade on de-novo priming responses to compounds within in vitro platforms. A regulatory competent human dendritic cell/T-cell coculture assay was used to model the effects of ICIs on de novo nitroso sulfamethoxazole- and sulfapyridine (SP) (the sulfonamide component of SLZ) hydroxylamine-specific priming responses. The role of T cells in the pathogenesis of the observed reactions was explored in 3 patients through phenotypic characterization of SP/sulfapyridine hydroxylamine (SPHA)-responsive T-cell clones (TCC), and assessment of cross-reactivity and pathways of T-cell activation. Augmentation of the frequency of responding drug-specific T cells and intensity of the T-cell response was observed with PD-1/PD-L1 blockade. Monoclonal populations of SP- and SPHA-responsive T cells were isolated from all 3 patients. A core secretory effector molecule profile (IFN-γ, IL-13, granzyme B, and perforin) was identified for SP and SPHA-responsive TCC, which proceeded through Pi and hapten mechanisms, respectively. Data presented herein provides evidence that drug-responsive T cells are effectors of hypersensitivity reactions observed in oncology patients administered ICIs and SLZ. Perturbation of drug-specific T-cell priming is a plausible explanation for clinical observations of how an increased incidence of these adverse events is occurring

The Lantern, 2015-2016

• Ghosts • Going to China • 98% Guaranteed • Constellation/Boulevard • Prayer • The Little One • Burning • The Amber Macaroon • Becoming • Requiem • Construction Site • Thirteen Ways of Looking at a Dragon • Charlie • No Sleep • A Lesson in Physical Education • Statues • Who Can Love a Black Woman? • Apples • Fun Craft • The Door at Midnight • Eve as a Book in the Bible • Boys • Diamond Heart • To Apollo • Joanne and Her July Garden • Option A, 1936 • Young White Girls, Hollow Bodies, and Home • Mama\u27s Stance on Sugar • The Mariana Trench • Hurricane • Part of the Job • Avenue H Blues • Hour of Nones • Send Toilet Paper • Grave Robbing • Wild Turkey • The Creek • Let\u27s Go for a Walk • Deaconess • Border of Love • Your Father, Rumpelstiltskin • Purchasing Poplars • Red Tatters • Sunken • Whispers • Existence • God Took a Cigarette Break with Police Officers • Martian Standoff • In the Headlights • It\u27s a Subtle Thing • Dear Kent • Hanako-san • A Brief Interlude • On Fencing, Gummy Worms, and my Inescapable Fear of Living in the Moment • Stolen Soul • Block • Mortem Mei Fratris • Kalki • Lake Placid • Atom and Eve • The Baerie Queene • Gladston • Soldiers at Gettysburg • Pattern • Foliage • Mass Media • Arrow • Move Out • Wanderers • Riverside Gardenhttps://digitalcommons.ursinus.edu/lantern/1182/thumbnail.jp

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

A Toxicological Framework for the Prioritization of Children’s Safe Product Act Data

In response to concerns over hazardous chemicals in children’s products, Washington State passed the Children’s Safe Product Act (CSPA). CSPA requires manufacturers to report the concentration of 66 chemicals in children’s products. We describe a framework for the toxicological prioritization of the ten chemical groups most frequently reported under CSPA. The framework scores lifestage, exposure duration, primary, secondary and tertiary exposure routes, toxicokinetics and chemical properties to calculate an exposure score. Four toxicological endpoints were assessed based on curated national and international databases: reproductive and developmental toxicity, endocrine disruption, neurotoxicity and carcinogenicity. A total priority index was calculated from the product of the toxicity and exposure scores. The three highest priority chemicals were formaldehyde, dibutyl phthalate and styrene. Elements of the framework were compared to existing prioritization tools, such as the United States Environmental Protection Agency’s (EPA) ExpoCast and Toxicological Prioritization Index (ToxPi). The CSPA framework allowed us to examine toxicity and exposure pathways in a lifestage-specific manner, providing a relatively high throughput approach to prioritizing hazardous chemicals found in children’s products

Prophage Induction and Differential RecA and UmuDAb Transcriptome Regulation in the DNA Damage Responses of <i>Acinetobacter baumannii</i> and <i>Acinetobacter baylyi</i>

<div><p>The SOS response to DNA damage that induces up to 10% of the prokaryotic genome requires RecA action to relieve LexA transcriptional repression. In <i>Acinetobacter</i> species, which lack LexA, the error-prone polymerase accessory UmuDAb is instead required for <i>ddrR</i> induction after DNA damage, suggesting it might be a LexA analog. RNA-Seq experiments defined the DNA damage transcriptome (mitomycin C-induced) of wild type, <i>recA</i> and <i>umuDAb</i> mutant strains of both <i>A. baylyi</i> ADP1 and <i>A. baumannii</i> ATCC 17978. Of the typical SOS response genes, few were differentially regulated in these species; many were repressed or absent. A striking 38.4% of all ADP1 genes, and 11.4% of all 17978 genes, were repressed under these conditions. In <i>A. baylyi</i> ADP1, 66 genes (2.0% of the genome), including a CRISPR/Cas system, were DNA damage-induced, and belonged to four regulons defined by differential use of <i>recA</i> and <i>umuDAb</i>. In <i>A. baumannii</i> ATCC 17978, however, induction of 99% of the 152 mitomycin C-induced genes depended on <i>recA</i>, and only 28 of these genes required <i>umuDAb</i> for their induction. 90% of the induced <i>A. baumannii</i> genes were clustered in three prophage regions, and bacteriophage particles were observed after mitomycin C treatment. These prophages encoded <i>esvI</i>, <i>esvK1</i>, and <i>esvK2</i>, ethanol-stimulated virulence genes previously identified in a <i>Caenorhabditis elegans</i> model, as well as error-prone polymerase alleles. The induction of all 17978 error-prone polymerase alleles, whether prophage-encoded or not, was <i>recA</i> dependent, but only these DNA polymerase V-related genes were de-repressed in the <i>umuDAb</i> mutant in the absence of DNA damage. These results suggest that both species possess a robust and complex DNA damage response involving both <i>recA-</i>dependent and <i>recA</i>-independent regulons, and further demonstrates that although <i>umuDAb</i> has a specialized role in repressing error-prone polymerases, additional regulators likely participate in these species' transcriptional response to DNA damage.</p></div

RT-qPCR experiments indicate that <i>umuDAb</i> is required for repression of error-prone polymerase components, not all DNA damage-induced genes.

<p>Delta Cq values from RT-qPCR experiments measuring expression of selected <i>A. baumannii</i> ATCC 17978 genes demonstrates the repressing activity of UmuDAb only for error prone polymerase components. The expression of each gene in both wild type and <i>umuDAb</i> null mutant is shown, with gene identity and A1S number listed on the x axis. Each gene was assayed in one RT-qPCR experiment (plate), with error bars indicating standard error of the mean from technical triplicates of biological triplicates.</p